Opium is a key material that is used in the production of morphine, codeine, thebaine and narcotine. Moreover, it is the only source for narcotine. Opium is obtained by cutting the unripe pods of Papaver Somniferum, then collecting the resulting fluid and drying the fluid under ambient conditions. Opium is typically obtained in loaves that are individually wrapped in paper and is a black, tarry material with a characteristic odor.
A major problem is the ability to efficiently and effectively separate the principal alkaloids as well as separate the principal alkaloids from the opium residue. There are a number of methods for separating opium into the principal alkaloids, i.e., morphine, codeine, oripavine, thebaine, papaverine and narcotine. However, all of these techniques are vastly improved by starting with material that is rich in the principal alkaloids with minimal opium residue and other alkaloids. The most common process to separate narcotic alkaloids, which includes morphine, codeine, oripavine, thebaine, papaverine and narcotine (noscapine), is by solvent extraction. Separation includes both purification as well as color removal. The separated narcotic alkaloids are then purified by carbon adsorption and precipitation.
One specific example of this type of modified solvent extraction is found in U.S. Pat. No. 6,054,584 issued to Ma, et al. on Apr. 25, 2000, which discloses a process for extracting only morphine from opium wherein the opium is dissolved in a basic alcoholic solution. The basic alcoholic solution is then filtered and the alcohol is removed from the filtrate to leave a residue. The residue is then extracted with a basic aqueous solution having a pH of at least 11. The basic aqueous solution may be filtered to remove any solid matter remaining after the aqueous extraction step, and then is stirred with a sufficient amount of salt to avoid the formation of an emulsion. The basic aqueous solution or filtrate is then extracted with benzene or toluene. Next, the pH of the basic aqueous filtrate is adjusted to a pH of between 8.5 to 9.5 that allows the morphine to precipitate for recovery.
There are a number of different ways to achieve adsorption besides the use of carbon. One way to achieve adsorption is through ion exchange. Yet another way to achieve adsorption is through polar interaction or normal phase adsorption. Still, yet another way to achieve adsorption is through separating alkaloids from other components based on molecular size by utilizing a membrane.
Another major method for processing opium to separate the principal alkaloids is based on dispersion of opium in water, which is then followed by extraction with hydrochloric acid. This then is followed by separation of the insoluble material with plate-and-frame filtration. This is then followed by separation of morphine and codeine from the other principal alkaloids by extraction with chloroform. The aqueous morphine and codeine stream is treated with lime to remove meconic acid. Morphine is then purified using multiple recrystallizations. Morphine and codeine are then separated by extraction with toluene, then the aqueous morphine stream is extracted with fusel oil. The remaining alkaloids are separated from the chloroform by acid extraction and evaporation. The narcotine, papaverine and thebaine are then obtained by fractional crystallization.
The preferred method for separating the principal alkaloids is by using preparative liquid chromatography. This method includes loading a stationary phase media into a chromatographic column, feeding a crude narcotic alkaloid solution into the chromatographic column, applying at least one mobile phase to the chromatographic column, and recovering at least one narcotic alkaloid eluate from the chromatographic column. This method is disclosed in International Patent Application No. WO03074526 that was published on Sep. 12, 2003, which is incorporated herein by reference in its entirety.
The present invention is directed to overcoming one or more of the problems set forth above.